Schizosaccharomyces pombe KAT5 contributes to resection and repair of a DNA double-strand break

Chromatin remodeling is essential for effective repair of a DNA double-strand break (DSB). KAT5 (Schizosaccharomyces pombe Mst1, human TIP60) is a MYST family histone acetyltransferase conserved from yeast to humans that coordinates various DNA damage response activities at a DNA DSB, including histone remodeling and activation of the DNA damage checkpoint. In S. pombe, mutations in mst1⁺ causes sensitivity to DNA damaging drugs. Here we show that Mst1 is recruited to DSBs. Mutation of mst1⁺ disrupts recruitment of repair proteins and delays resection. These defects are partially rescued by deletion of pku70, which has been previously shown to antagonize repair by homologous recombination (HR). These phenotypes of mst1 are similar to pht1-4KR, a nonacetylatable form of histone variant H2A.Z, which has been proposed to affect resection. Our data suggest that Mst1 functions to direct repair of DSBs toward HR pathways by modulating resection at the DSB.     

Surgical resection as a predictor of cancer-specific survival by stage at diagnosis and cancer type,United States, 2006–2015

BackgroundWhen solid tumors are amenable to definitive resection, clinical outcomes are generally superior to when those tumors are inoperable. However, the population-level cancer survival benefit of eligibility for surgery by cancer stage has not yet been quantified.MethodsUsing Surveillance, Epidemiology and End Results data allowing us to identify patients who were deemed eligible for and received surgical resection, we examined the stage-specific association of surgical resection with 12-year cancer-specific survival. The 12-year endpoint was selected to maximize follow-up time and thereby minimize the influence of lead time bias.ResultsAcross a variety of solid tumor types, earlier stage at diagnosis allowed for surgical intervention at a much higher rate than later-stage diagnosis. At every stage, surgical intervention was associated with a substantially higher rate of 12-year cancer-specific survival, with absolute differences of up to 51% for stage I, 51% for stage II, and 44% for stage III cancer, and stage-specific mortality relative risks of 3.6, 2.4, and 1.7, respectively.ConclusionsDiagnosis of solid cancers in early stages often enables surgical resection, which reduces the risk of death from cancer. Receipt of surgical resection is an informative endpoint that is strongly associated with long-term cancer-specific survival at every stage.     

Sequence and chromatin features guide DNA double-strand break resection initiation

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Mechanisms of helicase activated DNA end resection in bacteria

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RNA-DNA hybrids prevent resection at dysfunctional telomeres

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